Immune responses against oxidative stress-derived antigens are associated with increased circulating tumor necrosis factor-α in heavy drinkers

Vidali, Matteo; Hietala, Johanna; Occhino, G.; Ivaldi, A.; Sutti, Salvatore; Niemelä, Onni; Albano, Emanuele

doi:10.1016/j.freeradbiomed.2008.04.012

Cited by 41 publications

(35 citation statements)

References 33 publications

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“…Similar antibodies have also been observed in ~40% of adult NAFLD patients, as well as in subjects with advanced alcoholic liver disease (ALD) and chronic hepatitis C, two other liver diseases characterized by the involvement of oxidative stress (26,27,(33)(34)(35)(36). Moreover, ~35% of ALD patients also have circulating CD4…”

Section: Discussionmentioning

confidence: 57%

“…Several lines of evidence in ALD indicate the involvement of immunological mechanisms in fuelling hepatic inflammation during the progression of the disease (27). In particular, we have observed that heavy drinkers with high circulating levels of oxidative stress-induced antibodies have a 5-fold higher prevalence of elevated plasma TNF-· levels and 11-fold greater risk of advanced ALD than heavy drinkers with these antibodies within the control range (26).…”

Section: Discussionmentioning

confidence: 69%

“…In contrast to adult NAFLD, we did not observe any significant association between the presence of anti-MDA-HSA antibodies and the severity of fibrosis. This might be due to the low prevalence of extensive fibrosis in the population sample investigated (27).…”

Section: Discussionmentioning

confidence: 92%

“…MDA adducted with human serum albumin (MDA-HSA) was prepared by reacting for 2 h at 37˚C 2 mg/ml HSA with 100 mmol/l MDA as previously reported (27). For the evaluation of immune response induced by oxidative stress polystyrene microwell plates for enzyme-linked immunosorbent assay (ELISA) (Nunc-Immuno Maxi-Sorb, Nunc, S/A, Roskilde, Denmark) were coated for 4 h at 37˚C with 0.05 mg/ml of either modified or native HSA solubilised in 0.1 M bicarbonate buffer, pH 9.6.…”

Section: Measurement Of Antibody Titres Against Malondialdehydederivementioning

confidence: 99%

“…Human sera (0.20 ml, dilution 1:50 in the coating buffer) were added in duplicate and incubated for 1 h at 37˚C. After washing three times with PBS-0.25% Triton X-100, antibody binding was revealed using peroxidaselinked goat anti-human IgG (dilution 1:6,000) (Dako S.P.A., Milano, Italy) as previously described (27). The results were expressed by subtracting background reactivity from unmodified HSA.…”

Section: Measurement Of Antibody Titres Against Malondialdehydederivementioning

confidence: 99%

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Oxidative stress parameters in paediatric non-alcoholic fatty liver disease

Nobili

Parola

Alisi³

et al. 2010

Int J Mol Med

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Abstract.We have investigated the presence and the possible clinical implications of oxidative stress in children with nonalcoholic fatty liver disease (NAFLD). The present study was an observational study of oxidative stress parameters in the progression of paediatric NAFLD. We observed the role of oxidative stress in children diagnosed with NAFLD by evaluating: serum protein carbonyls, hepatic expression of 8-hydroxy-2-deoxyguanosine (8-OHG), and circulating antibody against malondialdehyde adducted human serum albumin (MDA-HSA). Forty consecutive children with biopsy-proven NAFLD (27 male; 13 female) referred to Bambino Gesù Children's Hospital, Rome, Italy, from January 2007 to April 2008 were included in the study. Serum variations of protein carbonyls, 8-OHG, and circulating antibody against MDA-HSA were evaluated. Elevated protein carbonyls were evident in 33 subjects (83%) irrespective of obesity and insulin resistance. Moreover, liver biopsies of NAFLD patients positive for circulating protein carbonyls also showed a significant increase in the nuclear staining for 8-OHG (p=0.006; 95% CI 3.1-17.7). Anti-MDA-HSA IgG above control threshold was detected in 25 (63%) children. Although protein carbonyl levels were unrelated with disease severity, patients with elevated anti-MDA-HSA IgG had scores for lobular inflammation significantly higher (p=0.019) than subjects with antibodies within the control range, while steatosis, hepatocyte ballooning and fibrosis were similar. High anti-MDA-HSA reactivity was also associated with a 13-fold increased risk (OR=12.9; 95% CI 1.5-113.8; p=0.013) of a NAFLD activity score (NAS) ≥5. These results demonstrate that oxidative stress has an high prevalence in children with NAFLD and is associated with an increased severity of steatohepatitis.

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